Maturation of the Cardiac Autonomic Nervous System Activity in Children and Adolescents

Lisette M Harteveld, Ineke Nederend, Arend D J Ten Harkel, Nienke M Schutte, Susanne R de Rooij, Tanja G M Vrijkotte, Helena Oldenhof, Arne Popma, Lucres M C Jansen, Jill Suurland, Hanna Swaab, Eco J C de Geus, FemNAT‐CD collaborators *, Martin Prätzlich, Katharina Ackermann, Rosalind Baker, Molly Batchelor, Sarah Baumann, Anka Bernhard, Roberta Clanton, Dimitris Dikeos, Roberta Dochnal, Lynn Valérie Fehlbaum, Aranzazu Fernández-Rivas, Karen Gonzalez, Maider González de Artaza-Lavesa, Silvina Guijarro, Malou Gundlach, Beate Herpertz-Dahlmann, Amaia Hervas, Linda Kersten, Gregor Kohls, Angeliki Konsta, Helen Lazaratou, Iñaki Kerexeta-Lizeaga, Anne Martinelli, Tisse van Nimwegen, Ignazio Puzzo, Nora Maria Raschle, Jack Rogers, Réka Siklósi, Areti Smaragdi, Martin Steppan, Stephane De Brito, Graeme Fairchild, Meinhard Kieser, Kerstin Konrad, Christine Freitag, Christina Stadler, Lisette M Harteveld, Ineke Nederend, Arend D J Ten Harkel, Nienke M Schutte, Susanne R de Rooij, Tanja G M Vrijkotte, Helena Oldenhof, Arne Popma, Lucres M C Jansen, Jill Suurland, Hanna Swaab, Eco J C de Geus, FemNAT‐CD collaborators *, Martin Prätzlich, Katharina Ackermann, Rosalind Baker, Molly Batchelor, Sarah Baumann, Anka Bernhard, Roberta Clanton, Dimitris Dikeos, Roberta Dochnal, Lynn Valérie Fehlbaum, Aranzazu Fernández-Rivas, Karen Gonzalez, Maider González de Artaza-Lavesa, Silvina Guijarro, Malou Gundlach, Beate Herpertz-Dahlmann, Amaia Hervas, Linda Kersten, Gregor Kohls, Angeliki Konsta, Helen Lazaratou, Iñaki Kerexeta-Lizeaga, Anne Martinelli, Tisse van Nimwegen, Ignazio Puzzo, Nora Maria Raschle, Jack Rogers, Réka Siklósi, Areti Smaragdi, Martin Steppan, Stephane De Brito, Graeme Fairchild, Meinhard Kieser, Kerstin Konrad, Christine Freitag, Christina Stadler

Abstract

Background Despite the increasing interest in cardiac autonomic nervous activity, the normal development is not fully understood. The main aim was to determine the maturation of different cardiac sympathetic-(SNS) and parasympathetic nervous system (PNS) activity parameters in healthy patients aged 0.5 to 20 years. A second aim was to determine potential sex differences. Methods and Results Five studies covering the 0.5- to 20-year age range provided impedance- and electrocardiography recordings from which heart rate, different PNS-parameters (eg, respiratory sinus arrhythmia) and an SNS-parameter (pre-ejection period) were collected. Age trends were computed in the mean values across 12 age-bins and in the age-specific variances. Age was associated with changes in mean and variance of all parameters. PNS-activity followed a cubic trend, with an exponential increase from infancy, a plateau phase during middle childhood, followed by a decrease to adolescence. SNS-activity showed a more linear trend, with a gradual decrease from infancy to adolescence. Boys had higher SNS-activity at ages 11 to 15 years, while PNS-activity was higher at 5 and 11 to 12 years with the plateau level reached earlier in girls. Interindividual variation was high at all ages. Variance was reasonably stable for SNS- and the log-transformed PNS-parameters. Conclusions Cardiac PNS- and SNS-activity in childhood follows different maturational trajectories. Whereas PNS-activity shows a cubic trend with a plateau phase during middle childhood, SNS-activity shows a linear decrease from 0.5 to 20 years. Despite the large samples used, clinical use of the sex-specific centile and percentile normative values is modest in view of the large individual differences, even within narrow age bands.

Keywords: autonomic nervous system; development; heart rate variability; pediatrics; sympathetic nerve activity.

Conflict of interest statement

None.

Figures

FIGURE 1. Scatterplots of age‐related heart rate…
FIGURE 1. Scatterplots of age‐related heart rate and pre‐ejection period for boys and girls with cubic and linear smoothing of median.
ABCD indicates the Amsterdam Born Children and their Development study; FemNAT‐CD, the Neurobiology and Treatment of Adolescent Female Conduct Disorder study; MINDS, the Mother‐Infant Neurodevelopment Study; and NTR, Netherlands Twin Register; and PEP, pre‐ejection period.
FIGURE 2. Scatterplots of age‐related heart rate…
FIGURE 2. Scatterplots of age‐related heart rate variability with cubic smoothing of median.
ABCD indicates the Amsterdam Born Children and their Development study; FemNAT‐CD, the Neurobiology and Treatment of Adolescent Female Conduct Disorder study; MINDS, the Mother‐Infant Neurodevelopment Study; NTR, Netherlands Twin Register; RSA, respiratory sinus arrhythmia; RMSSD, root mean square of successive differences between normal sinus beats; and SDNN, SD of the inter‐beat interval of normal sinus beats.
FIGURE 3. Histograms of SDs per age…
FIGURE 3. Histograms of SDs per age group for heart rate, pre‐ejection period, respiratory sinus arrhythmia, root mean square of successive differences between normal sinus beats and SD of the inter‐beat interval of normal sinus beats.
HR indicates heart rate; PEP, pre‐ejection period; RMSSD, root mean square of successive differences; RSA, respiratory sinus arrhythmia (set at zero); and SDNN, SD of the inter‐beat intervals of normal sinus beats.

References

    1. Gibbons CH. Basics of autonomic nervous system function. Handb Clin Neurol. 2019;160:407–418.
    1. de Geus EJC, Gianaros PJ, Brindle RC, Jennings JR, Berntson GG. Should heart rate variability be "corrected" for heart rate? Biological, quantitative, and interpretive considerations. Psychophysiol. 2019;56:e13287.
    1. Nederend I, Ten Harkel ADJ, Blom NA, Berntson GG, de Geus EJC. Impedance cardiography in healthy children and children with congenital heart disease: Improving stroke volume assessment. Int J Psychophysiol. 2017;120:136–147.
    1. Nederend I, Schutte NM, Bartels M, Ten Harkel AD, de Geus EJ. Heritability of heart rate recovery and vagal rebound after exercise. Eur J Appl Physiol. 2016;116:2167–2176.
    1. Berntson GG, Cacioppo JT, Quigley KS. Autonomic cardiac control. I. Estimation and validation from pharmacological blockades. Psychophysiol. 1994;31:572–585.
    1. Goedhart AD, Kupper N, Willemsen G, Boomsma DI, de Geus EJ. Temporal stability of ambulatory stroke volume and cardiac output measured by impedance cardiography. Biol Psychol. 2006;72:110–117.
    1. Harris WS, Schoenfeld CD, Weissler AM. Effects of adrenergic receptor activation and blockade on the systolic preejection period, heart rate, and arterial pressure in man. J Clin Invest. 1967;46:1704–1714.
    1. Houtveen JH, Groot PF, Geus EJ. Effects of variation in posture and respiration on RSA and pre‐ejection period. Psychophysiol. 2005;42:713–719.
    1. Krzemiński K, Kruk B, Nazar K, Ziemba AW, Cybulski G, Niewiadomski W. Cardiovascular, metabolic and plasma catecholamine responses to passive and active exercises. J Physiol Pharmacol. 2000;51:267–278.
    1. Kupper N, Willemsen G, Boomsma DI, de Geus EJ. Heritability of indices for cardiac contractility in ambulatory recordings. J Cardiovasc Electrophysiol. 2006;17:877–883.
    1. Mezzacappa ES, Kelsey RM, Katkin ES. The effects of epinephrine administration on impedance cardiographic measures of cardiovascular function. Int J Psychophysiol. 1999;31:189–196. DOI: 10.1016/S0167-8760(98)00058-0.
    1. Miyamoto Y, Higuchi J, Abe Y, Hiura T, Nakazono Y, Mikami T. Dynamics of cardiac output and systolic time intervals in supine and upright exercise. J Appl Physiol Respir Environ Exerc Physiol. 1983;55:1674–1681. DOI: 10.1152/jappl.1983.55.6.1674.
    1. Nelesen RA, Shaw R, Ziegler MG, Dimsdale JE. Impedance cardiography‐derived hemodynamic responses during baroreceptor testing with amyl nitrite and phenylephrine: a validity and reliability study. Psychophysiol. 1999;36:105–108. DOI: 10.1017/S0048577299971500.
    1. Newlin DB, Levenson RW. Pre‐ejection period: measuring beta‐adrenergic influences upon the heart. Psychophysiol. 1979;16:546–553. DOI: 10.1111/j.1469-8986.1979.tb01519.x.
    1. Richter M, Gendolla GH. The heart contracts to reward: monetary incentives and preejection period. Psychophysiol. 2009;46:451–457. DOI: 10.1111/j.1469-8986.2009.00795.x.
    1. Schachinger H, Weinbacher M, Kiss A, Ritz R, Langewitz W. Cardiovascular indices of peripheral and central sympathetic activation. Psychosom Med. 2001;63:788–796. DOI: 10.1097/00006842-200109000-00012.
    1. Sherwood A, Allen MT, Obrist PA, Langer AW. Evaluation of beta‐adrenergic influences on cardiovascular and metabolic adjustments to physical and psychological stress. Psychophysiol. 1986;23:89–104. DOI: 10.1111/j.1469-8986.1986.tb00602.x.
    1. Smith JJ, Muzi M, Barney JA, Ceschi J, Hayes J, Ebert TJ. Impedance‐derived cardiac indices in supine and upright exercise. Ann Biomed Eng. 1989;17:507–515.
    1. Svedenhag J, Martinsson A, Ekblom B, Hjemdahl P. Altered cardiovascular responsiveness to adrenaline in endurance‐trained subjects. Acta Physiol Scand. 1986;126:539–550. DOI: 10.1111/j.1748-1716.1986.tb07853.x.
    1. Vrijkotte TG, van Doornen LJ, de Geus EJ. Overcommitment to work is associated with changes in cardiac sympathetic regulation. Psychosom Med. 2004;66:656–663. DOI: 10.1097/01.psy.0000138283.65547.78.
    1. Williams PD, Puddey IB, Beilin LJ, Vandongen R. Genetic influences on plasma catecholamines in human twins. J Clin Endocrinol Metab. 1993;77:794–799.
    1. Winzer A, Ring C, Carroll D, Willemsen G, Drayson M, Kendall M. Secretory immunoglobulin a and cardiovascular reactions to mental arithmetic, cold pressor, and exercise: effects of beta‐adrenergic blockade. Psychophysiol. 1999;36:591–601. DOI: 10.1111/1469-8986.3650591.
    1. Billman GE. Heart rate variability ‐ a historical perspective. Front Physiol. 2011;2:86. DOI: 10.3389/fphys.2011.00086.
    1. Dollar JM, Calkins SD, Berry NT, Perry NB, Keane SP, Shanahan L, Wideman L. Developmental patterns of respiratory sinus arrhythmia from toddlerhood to adolescence. Dev Psychol. 2020;56:783–794. DOI: 10.1037/dev0000894.
    1. Gower AL, Crick NR. Baseline autonomic nervous system arousal and physical and relational aggression in preschool: The moderating role of effortful control. Int J Psychophysiol. 2011;81:142–151. DOI: 10.1016/j.ijpsycho.2011.06.001.
    1. Ohuchi H, Negishi J, Miyake A, Sakaguchi H, Miyazaki A, Yamada O. Long‐term prognostic value of cardiac autonomic nervous activity in postoperative patients with congenital heart disease. Int J Cardiol. 2011;151:296–302. DOI: 10.1016/j.ijcard.2010.05.062.
    1. Alkon A, Boyce WT, Davis NV, Eskenazi B. Developmental changes in autonomic nervous system resting and reactivity measures in latino children from 6 to 60 months of age. J Dev Behav Pediatr. 2011;32:668–677. DOI: 10.1097/DBP.0b013e3182331fa6.
    1. Bornstein MH, Suess PE. Child and mother cardiac vagal tone: Continuity, stability, and concordance across the first 5 years. Dev Psychol. 2000;36:54–65. DOI: 10.1037/0012-1649.36.1.54.
    1. El‐Sheikh M. Stability of respiratory sinus arrhythmia in children and young adolescents: a longitudinal examination. Dev Psychobiol. 2005;46:66–74. DOI: 10.1002/dev.20036.
    1. El‐Sheikh M, Hinnant JB, Philbrook LE. Trajectories of sleep and cardiac sympathetic activity indexed by pre‐ejection period in childhood. J Sleep Res. 2017;26:578–586. DOI: 10.1111/jsr.12491.
    1. Gatzke‐Kopp L, Ram N. Developmental dynamics of autonomic function in childhood. Psychophysiol. 2018;55:e13218.
    1. Hinnant JB, Elmore‐Staton L, El‐Sheikh M. Developmental trajectories of respiratory sinus arrhythmia and preejection period in middle childhood. Dev Psychobiol. 2011;53:59–68.
    1. Jewell SL, Suk HW, Luecken LJ. Respiratory sinus arrhythmia: modeling longitudinal change from 6 weeks to 2 years of age among low‐income Mexican Americans. Dev Psychobiol. 2018;60:232–238.
    1. Longin E, Dimitriadis C, Shazi S, Gerstner T, Lenz T, Konig S. Autonomic nervous system function in infants and adolescents: impact of autonomic tests on heart rate variability. Pediatr Cardiol. 2009;30:311–324.
    1. Matthews KA, Salomon K, Kenyon K, Allen MT. Stability of children's and adolescents' hemodynamic responses to psychological challenge: a three‐year longitudinal study of a multiethnic cohort of boys and girls. Psychophysiol. 2002;39:826–834.
    1. Pang KC, Beauchaine TP. Longitudinal patterns of autonomic nervous system responding to emotion evocation among children with conduct problems and/or depression. Dev Psychobiol. 2013;55:698–706.
    1. Patriquin MA, Lorenzi J, Scarpa A, Bell MA. Developmental trajectories of respiratory sinus arrhythmia: associations with social responsiveness. Dev Psychobiol. 2014;56:317–326.
    1. Shader TM, Gatzke‐Kopp LM, Crowell SE, Jamila Reid M, Thayer JF, Vasey MW, Webster‐Stratton C, Bell Z, Beauchaine TP. Quantifying respiratory sinus arrhythmia: effects of misspecifying breathing frequencies across development. Dev Psychopathol. 2018;30:351–366.
    1. Sheinkopf SJ, Levine TP, McCormick CEB, Puggioni G, Conradt E, Lagasse LL, Lester BM. Developmental trajectories of autonomic functioning in autism from birth to early childhood. Biol Psychol. 2019;142:13–18.
    1. Massin M, von Bernuth G. Normal ranges of heart rate variability during infancy and childhood. Pediatr Cardiol. 1997;18:297–302.
    1. Michels N, Clays E, De Buyzere M, Huybrechts I, Marild S, Vanaelst B, De Henauw S, Sioen I. Determinants and reference values of short‐term heart rate variability in children. Eur J Appl Physiol. 2013;113:1477–1488. DOI: 10.1007/s00421-012-2572-9.
    1. Silvetti MS, Drago F, Ragonese P. Heart rate variability in healthy children and adolescents is partially related to age and gender. Int J Cardiol. 2001;81:169–174. DOI: 10.1016/S0167-5273(01)00537-X.
    1. van den Berg ME, Rijnbeek PR, Niemeijer MN, Hofman A, van Herpen G, Bots ML, Hillege H, Swenne CA, Eijgelsheim M, Stricker BH, et al. Normal values of corrected heart‐rate variability in 10‐second electrocardiograms for all ages. Front Physiol. 2018;10:424. DOI: 10.3389/fphys.2018.00424.
    1. Shaffer F, Ginsberg JP. An overview of heart rate variability metrics and norms. Front Public Health. 2017;5:258. DOI: 10.3389/fpubh.2017.00258.
    1. Pereyra PM, Zhang W, Schmidt M, Becker LE. Development of myelinated and unmyelinated fibers of human vagus nerve during the first year of life. J Neurol Sci. 1992;110:107–113. DOI: 10.1016/0022-510X(92)90016-E.
    1. Lenard Z, Studinger P, Mersich B, Kocsis L, Kollai M. Maturation of cardiovagal autonomic function from childhood to young adult age. Circulation. 2004;110:2307–2312. DOI: 10.1161/01.CIR.0000145157.07881.A3.
    1. Gasior JS, Sacha J, Jelen PJ, Pawlowski M, Werner B, Dabrowski MJ. Interaction between heart rate variability and heart rate in pediatric population. Front Physiol. 2015;6:385. DOI: 10.3389/fphys.2015.00385.
    1. Jarrin DC, McGrath JJ, Poirier P, Seguin L, Tremblay RE, Montplaisir JY, Paradis G, Seguin JR. Short‐term heart rate variability in a population‐based sample of 10‐year‐old children. Pediatr Cardiol. 2015;36:41–48. DOI: 10.1007/s00246-014-0962-y.
    1. Patural H, Pichot V, Flori S, Giraud A, Franco P, Pladys P, Beuchee A, Roche F, Barthelemy JC. Autonomic maturation from birth to 2 years: normative values. Heliyon. 2019;5:e01300. DOI: 10.1016/j.heliyon.2019.e01300.
    1. Fukuba Y, Sato H, Sakiyama T, Yamaoka Endo M, Yamada M, Ueoka H, Miura A, Koga S. Autonomic nervous activities assessed by heart rate variability in pre‐ and post‐adolescent Japanese. J Physiol Anthropol. 2009;28:269–273. DOI: 10.2114/jpa2.28.269.
    1. Seppala S, Laitinen T, Tarvainen MP, Tompuri T, Veijalainen A, Savonen K, Lakka T. Normal values for heart rate variability parameters in children 6–8 years of age: the panic study. Clin Physiol Funct Imaging. 2014;34:290–296.
    1. Coupal KE, Heeney ND, Hockin BCD, Ronsley R, Armstrong K, Sanatani S, Claydon VE. Pubertal hormonal changes and the autonomic nervous system: potential role in pediatric orthostatic intolerance. Front Neurosci. 2019;13:1197. DOI: 10.3389/fnins.2019.01197.
    1. Gao Y, Raine A, Dawson ME, Venables PH, Mednick SA. Development of skin conductance orienting, habituation, and reorienting from ages 3 to 8 years: a longitudinal latent growth curve analysis. Psychophysiol. 2007;44:855–863. DOI: 10.1111/j.1469-8986.2007.00564.x.
    1. Gutin B, Howe C, Johnson MH, Humphries MC, Snieder H, Barbeau P. Heart rate variability in adolescents: relations to physical activity, fitness, and adiposity. Med Sci Sports Exerc. 2005;37:1856–1863. DOI: 10.1249/01.mss.0000175867.98628.27.
    1. Hu MX, Lamers F, de Geus EJ, Penninx BW. Influences of lifestyle factors on cardiac autonomic nervous system activity over time. Prev Med. 2017;94:12–19. DOI: 10.1016/j.ypmed.2016.11.003.
    1. van Beijsterveldt CEM, Groen‐Blokhuis M, Hottenga JJ, Franić S, Hudziak JJ, Lamb D, Huppertz C, de Zeeuw E, Nivard M, Schutte N, et al. The Young Netherlands Twin Register (YNTR): longitudinal twin and family studies in over 70,000 children. Twin Res Hum Genet. 2013;16:252–267. DOI: 10.1017/thg.2012.118.
    1. Freitag CM, Konrad K, Stadler C, De Brito SA, Popma A, Herpertz SC, Herpertz‐Dahlmann B, Neumann I, Kieser M, Chiocchetti AG, et al. Conduct disorder in adolescent females: current state of research and study design of the FemNAT‐CD consortium. Eur Child Adolesc Psychiatry. 2018;27:1077–1093. DOI: 10.1007/s00787-018-1172-6.
    1. Suurland J, van der Heijden KB, Smaling HJA, Huijbregts SCJ, van Goozen SHM, Swaab H. Infant autonomic nervous system response and recovery: associations with maternal risk status and infant emotion regulation. Dev Psychopathol. 2017;29:759–773. DOI: 10.1017/S0954579416000456.
    1. de Beer M, van Eijsden M, Vrijkotte TG, Gemke RJ. Early growth patterns and cardiometabolic function at the age of 5 in a multiethnic birth cohort: the ABCD study. BMC Pediatr. 2009;10:23. DOI: 10.1186/1471-2431-9-23.
    1. Riese H, Groot PF, van den Berg M, Kupper NH, Magnee EH, Rohaan EJ, Vrijkotte TG, Willemsen G, de Geus EJ. Large‐scale ensemble averaging of ambulatory impedance cardiograms. Behav Res Methods Instrum Comput. 2003;35:467–477. DOI: 10.3758/BF03195525.
    1. Schaffer L, Burkhardt T, Tomaske M, Schmidt S, Luzi F, Rauh M, Leone A, Beinder E. Effect of antenatal betamethasone administration on neonatal cardiac autonomic balance. Pediatr Res. 2010;68:286–291. DOI: 10.1203/PDR.0b013e3181ed0cf2.
    1. R Development Core Team . R: A language and Environment for Statistical Computing. 2019.
    1. Wickham H. Ggplot2: Elegant Graphics for Data Analysis. New York: Springer; 2016.
    1. Goedhart AD, Willemsen G, Houtveen JH, Boomsma DI, De Geus EJ. Comparing low frequency heart rate variability and preejection period: two sides of a different coin. Psychophysiol. 2008;45:1086–1090. DOI: 10.1111/j.1469-8986.2008.00710.x.
    1. Reyes del Paso GA, Langewitz W, Mulder LJ, van Roon A, Duschek S. The utility of low frequency heart rate variability as an index of sympathetic cardiac tone: a review with emphasis on a reanalysis of previous studies. Psychophysiol. 2013;50:477–487. DOI: 10.1111/psyp.12027.
    1. Cacioppo JT, Berntson GG, Binkley PF, Quigley KS, Uchino BN, Fieldstone A. Autonomic cardiac control. II. Noninvasive indices and basal response as revealed by autonomic blockades. Psychophysiol. 1994;31:586–598. DOI: 10.1111/j.1469-8986.1994.tb02351.x.
    1. Sherwood A, Allen MT, Fahrenberg J, Kelsey RM, Lovallo WR, van Doornen LJ. Methodological guidelines for impedance cardiography. Psychophysiol. 1990;27:1–23. DOI: 10.1111/j.1469-8986.1990.tb02171.x.
    1. Ferrara N, Komici K, Corbi G, Pagano G, Furgi G, Rengo C, Femminella GD, Leosco D, Bonaduce D. Beta‐adrenergic receptor responsiveness in aging heart and clinical implications. Front Physiol. 2014;4:396.
    1. von Holzen JJ, Capaldo G, Wilhelm M, Stute P. Impact of endo‐ and exogenous estrogens on heart rate variability in women: a review. Climacteric. 2016;19:222–228. DOI: 10.3109/13697137.2016.1145206.
    1. Brix N, Ernst A, Lauridsen LLB, Parner E, Stovring H, Olsen J, Henriksen TB, Ramlau‐Hansen CH. Timing of puberty in boys and girls: a population‐based study. Paediatr Perinat Epidemiol. 2019;33:70–78. DOI: 10.1111/ppe.12507.

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